Zafer Mai M, Hussein Amira F A, Al-Agamy Mohamed H, Radwan Hesham H, Hamed Samira M
Department of Microbiology and Immunology, Faculty of Pharmacy, Ahram Canadian University, Cairo, Egypt.
Clinical and Chemical Pathology Department, Faculty of Medicine, Cairo University, Cairo, Egypt.
Front Microbiol. 2021 Nov 22;12:736982. doi: 10.3389/fmicb.2021.736982. eCollection 2021.
has become a major challenge to clinicians worldwide due to its high epidemic potential and acquisition of antimicrobial resistance. This work aimed at investigating antimicrobial resistance determinants and their context in four extensively drug-resistant (XDR) NDM-producing clinical isolates collected between July and October 2020 from Kasr Al-Ainy Hospital, Cairo, Egypt. A total of 20 were collected and screened for acquired carbapenemases ( , and ) using PCR. Four NDM producer isolates were identified and selected for whole-genome sequencing, multilocus sequence typing, and resistome analysis. Antimicrobial susceptibility profiles were determined using disk diffusion and broth microdilution tests. All -positive isolates were XDR. Three isolates belonged to high-risk international clones (IC), namely, IC2 corresponding to ST570/1701 (M20) and IC9 corresponding to ST85/ST1089 (M02 and M11). For the first time, we report gene on the chromosome of an strain that belongs to sequence type ST164/ST1418. Together with , was bracketed by two copies of IS in ST85 isolates possibly facilitating co-transfer of amikacin and carbapenem resistance. A novel allele ( ) with an upstream IS element was identified in M19 (ST/CC164 and ST1418/CC234). genes harbored by M02 and M11 were uniquely interrupted by IS1008. Tn-associated was carried by M20. genes were preceded by IS element in M02 and M11. AbGRI3 was carried by M20 hosting the resistance genes (), (), , ant(3), , , (), and (). Nonsynonymous mutations were identified in the quinolone resistance determining regions ( and ) of all isolates. Resistance to colistin in M19 was accompanied by missense mutations in and genes. The current study provided an insight into the genomic background of XDR phenotype in recovered from patients in Egypt. WGS revealed strong association between resistance genes and diverse mobile genetic elements with novel insertion sites and genetic organizations.
由于其高流行潜力和获得性抗菌药物耐药性，这已成为全球临床医生面临的一项重大挑战。这项工作旨在调查2020年7月至10月期间从埃及开罗卡斯尔·艾尼医院收集的4株产NDM的广泛耐药（XDR）临床分离株中的抗菌药物耐药性决定因素及其背景。共收集了20株菌株，并使用PCR筛选获得性碳青霉烯酶（NDM、VIM和OXA）。鉴定出4株产NDM的分离株，并选择进行全基因组测序、多位点序列分型和耐药基因组分析。使用纸片扩散法和肉汤微量稀释法测定抗菌药物敏感性谱。所有NDM阳性分离株均为XDR。3株分离株属于高风险国际克隆（IC），即对应于ST570/1701（M20）的IC2和对应于ST85/ST1089（M02和M11）的IC9。我们首次报告在一株属于序列型ST164/ST1418的菌株染色体上发现blaNDM基因。在ST85分离株中，blaNDM与blaOXA-181被两个IS拷贝包围，这可能促进了阿米卡星和碳青霉烯耐药性的共同转移。在M19（ST/CC164和ST1418/CC234）中鉴定出一个带有上游IS元件的新型blaNDM等位基因（blaNDM-19）。M02和M11携带的blaNDM基因被IS1008独特地打断。M20携带Tn2006相关的blaNDM。M02和M11中的blaNDM基因之前有IS元件。M20携带AbGRI3，其携带耐药基因（blaTEM）、（blaSHV）、blaOXA-181、ant(3")、aac(6')-Ib-cr、aph(3')-IIIa、(blaDHA)、(blaCTX-M)。在所有分离株的喹诺酮耐药决定区（gyrA和parC）中鉴定出非同义突变。M19中对黏菌素的耐药性伴随着pmrB和pmrC基因中的错义突变。本研究深入了解了从埃及患者中分离出的XDR鲍曼不动杆菌表型的基因组背景。全基因组测序揭示了耐药基因与具有新插入位点和基因组织的多种移动遗传元件之间的强关联。
